It has been suggested that subjects with diabetes or impaired glucose tolerance (IGT) have a higher prevalence of hypertension than subjects with normal glucose tolerance (NGT). Both obesity and glucose intolerance are related to increased insulin resistance, hyperinsulinemia, and increased risk of hypertension. Moreover, patients with essential hypertension are insulin resistant and hyperinsulinemic. Thus, it has been postulated that insulin might be involved in the pathogenesis of hypertension. The incidence of hypertension by glucose tolerance was determined in 2784 Pima Indians without clinical proteinuria at baseline, and the associations between insulin treatment or endogenous insulin concentration and incidence of hypertension were examined among these subjects. Subjects with diabetes or IGT had a higher incidence of hypertension than did subjects with NGT. Among all diabetic subjects, exogenous insulin (insulin treatment) predicted subsequent hypertension. Among nondiabetic subjects, but not diabetic subjects treated with insulin, endogenous fasting insulin concentration predicted subsequent hypertension. Thus, these findings support the hypothesis that insulin plays a role in developing hypertension in non-diabetic Pima Indians.